Deconstructing the Form and Function of the TCR/CD3 Complex Michael S. Kuhns, Mark M. Davis, K. Christopher Garcia  Immunity  Volume 24, Issue 2, Pages 133-139 (February 2006) DOI: 10.1016/j.immuni.2006.01.006 Copyright © 2006 Elsevier Inc. Terms and Conditions

Figure 1 TCR/CD3 Complex Subunits and Intersubunit Interaction Sites (A) The “anatomy” of αβTCR/CD3 (left) and γδTCR/CD3 (right) complexes, showing extracellular, transmembrane, and intracellular regions. Interacting ionizable transmembrane residues are highlighted, with the acidic residues in the CD3 transmembrane regions colored red and the basic residues in the TCR transmembrane residues colored blue. The two acidic-one basic electrostatic interactions are depicted in the red to blue ovals. This figure is modified from the basic concepts presented by Wucherpfennig and colleagues (Call et al., 2002, 2005). (B) Putative extracellular CD3δε and CD3γε docking sites on the αβTCR. Surface-rendered models of the 2C TCR are shown with the α chain primarily in white and the β chain primarily in purple. CD3 docking sites previously proposed in the literature are highlighted as blue (Garcia et al., 1996), cyan (Garcia et al., 1996; Karaivanova et al., 1999; Kjer-Nielsen et al., 2003; Sun et al., 2004), green (Ghendler et al., 1998; Kjer-Nielsen et al., 2003; Sun et al., 2001, 2004), and orange (Sun et al., 2001). Immunity 2006 24, 133-139DOI: (10.1016/j.immuni.2006.01.006) Copyright © 2006 Elsevier Inc. Terms and Conditions

Figure 2 Possible Mechanisms of TCR/CD3 Signal Transduction Involving Extracellular Interactions An αβTCR/CD3 complex, with subunits colored as in Figure 1A, is presented binding a pMHC (gray). The numbered scenarios are fully explained in the main text. Similar mechanisms can be considered for γδTCR/CD3 complexes. Although the αβTCR/CD3 complex is shown in the conventional manner, with the CD3 heterodimers on opposite sides of the TCR, it is equally possible that the CD3 heterodimers are oriented adjacent to one another within the full TCR/CD3 complex. CD3ζζ has been omitted, because it lacks a significant extracellular domain, but it must be considered in future models as more information becomes available regarding the orientation of the extracellular domains of the CD3 heterodimers and the spatial relationship between the transmembrane ionizable residues and the extracellular domains. These five scenarios do not exhaust all of the mechanistic possibilities. Immunity 2006 24, 133-139DOI: (10.1016/j.immuni.2006.01.006) Copyright © 2006 Elsevier Inc. Terms and Conditions